Digital Commons Network^™

The Havcr1-Centric Host Factor Network Drives Zika Virus Vertical Transmission, Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

Center on Aging Staff Publications

Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via …

Parapneumonic Empyema Complicating Community-Acquired Pneumonia: Etiology In The Era Of Pneumococcal Vaccination And Role Of Molecular Diagnosis, Antonio C Arrieta, Stephanie Osborne, Lindsay R Grant, Bradford D Gessner, Anne J Blaschke, Kristina G Hulten, Delma J Nieves, Ashley Miller, Cody Bender, Raul Isturiz, Ronika Alexander, Shannon M Nielsen, Linda B Lamberth, Alejandro Cane, Adriano Arguedas

Faculty, Staff and Students Publications

Background: Impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal disease is well described; pneumococcus is infrequently identified by culture in pneumonia. Yield is higher when pleural fluid is cultured. Polymerase chain reaction (PCR) in pleural fluid samples improves pathogen identification, particularly in the case of S. pneumoniae.

Methods: Healthy children with empyema who underwent pleural fluid drainage were eligible. Demographics and PCV immunization status were collected. Blood/pleural fluid cultures were obtained. Pleural fluid samples were sent for PCR for pathogen. Serotyping was done by Neufeld-Quellung reaction on pneumococcus isolates, and PCR in culture negative cases.

Results: From December 2018 to …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Distinguishing Multisystem Inflammatory Syndrome In Children From Typhus Using Artificial Intelligence: Mis-C Versus Endemic Typhus (Ai-Met), Angela Chun, Abraham Bautista-Castillo, Isabella Osuna, Kristiana Nasto, Flor M Munoz, Gordon E Schutze, Sridevi Devaraj, Eyal Muscal, Marietta M De Guzman, Kristen Sexson Tejtel, Tiphanie P Vogel, Ioannis A Kakadiaris

Faculty, Staff and Students Publications

Background: The pandemic emergent disease multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease-19 infection can mimic endemic typhus. We aimed to use artificial intelligence (AI) to develop a clinical decision support system that accurately distinguishes MIS-C versus endemic typhus (MET).

Methods: Demographic, clinical, and laboratory features rapidly available following presentation were extracted for 133 patients with MIS-C and 87 patients hospitalized due to typhus. An attention module assigned importance to inputs used to create the 2-phase AI-MET. Phase 1 uses 17 features to arrive at a classification manually (MET-17). If the confidence level is not surpassed, 13 additional features …

Sociodemographic Differences In Logins And Engagement With The Electronic Health Coach Messaging Feature Of A Mobile App To Support Opioid And Stimulant Use Recovery: Results From A 1-Month Observational Study, Lindsey M Filiatreau, Hannah Szlyk, Alex T Ramsey, Erin Kasson, Xiao Li, Zhuoran Zhang, Patricia Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: Mobile health apps can serve as a critical tool in supporting the overall health of uninsured and underinsured individuals and groups who have been historically marginalized by the medical community and may be hesitant to seek health care. However, data on uptake and engagement with specific app features (eg, in-app messaging) are often lacking, limiting our ability to understand nuanced patterns of app use.

OBJECTIVE: This study aims to characterize sociodemographic differences in uptake and engagement with a smartphone app (uMAT-R) to support recovery efforts in a sample of individuals with opioid and stimulant use disorders in the Greater …

Epidemiologic Investigation Of Protozoa And Soil-Transmitted Helminths In Starr County, Texas, Lauren M Leining, Timothy A Erickson, Craig L Hanis, Cici Bauer, Maya D Murry, Eric L Brown, Rojelio Mejia, Sarah M Gunter

Faculty, Staff and Students Publications

The burden of pathogenic enteric protozoa and soil-transmitted helminths among impoverished populations living on the Texas-Mexico border is unclear. We conducted a cross-sectional study on an ongoing longitudinal cohort of 616 adults residing in Starr County, Texas. A total of 359 adults were screened for four protozoa and five soil-transmitted helminths by using real-time polymerase chain reaction. This analysis identified 48 (13.4%) participants who tested positive for Blastocystis sp., three (0.8%) who tested positive for Giardia intestinalis, and one (0.3%) who tested positive for Strongyloides stercoralis and was also coinfected with Blastocystis sp. Infection was significantly associated with age, a …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Prediction Of Hepatitis C Virus Perinatal Transmission In Pregnant Individuals With Hepatitis C Virus Infection, Grecio J Sandoval, George R Saade, Brenna L Hughes, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones, Mona Prasad

Faculty, Staff and Student Publications

Our objective was to develop a prediction model for hepatitis C virus (HCV) infection perinatal transmission to improve triage for neonatal follow-up. This was a secondary analysis of HCV antibody-positive participants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network multicenter observational study of HCV infection in pregnancy. Among 432 participants, the perinatal transmission rate was 6.0% (95% CI, 4.0-8.7%). The prediction model was developed and included two factors: maternal HCV RNA titer greater than 10 6 international units/mL and having had any antepartum bleeding. Using this model, the …

Statin Use Is Associated With Protection Against Acute Cholangitis In Patients With Primary Sclerosing Cholangitis: A Multicenter Retrospective Cohort Study, Chiraag Kulkarni, George Cholankeril, Touran Fardeen, Joseph Rathkey, Samir Khan, Soumya Murag, Robert Lerrigo, Ahmad Kamal, Ajitha Mannalithara, Prasun Jalal, Aijaz Ahmed, John Vierling, Aparna Goel, Sidhartha R Sinha

Faculty, Staff and Students Publications

Introduction: Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC.

Methods: This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression.

Results: The patients were predominantly male (68.7%) with a median age at enrollment of 48 …

Variability In Treatment Of Utis In Children With Genitourinary Anomalies In Children's Hospitals, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Sanyukta Desai, Pearl W Chang, Michael J Tchou, John M Morrison, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Cynthia Abou Zeid, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

Objective: In children with urinary tract anomalies, febrile urinary tract infections (UTIs) are associated with increased risks of sepsis, hospitalization, and kidney injury. However, the best treatment strategies are unknown. We aimed to describe antibiotic treatment practices and outcomes for UTIs in children with urinary tract anomalies and evaluate whether variability in UTI treatment exists between hospitals.

Methods: We conducted a multicenter retrospective cohort study of children seen in emergency departments (EDs) in 6 free-standing US children's hospitals from January 1, 2017, through December 31, 2018. We included children aged 0-17 years with an anatomic or functional urinary tract anomaly …

Postnatal Zika And Dengue Infection And Their Effects On Neurodevelopment Among Children Living In Rural Guatemala, Edwin J Asturias, Amy K Connery, Daniel Olson, Molly M Lamb, Alejandra Paniagua-Avila, Evan J Anderson, Chris Focht, Alison M Colbert, Muktha Natrajan, Jesse J Waggoner, Erin Scherer, D Mirella Calvimontes, Guillermo A Bolaños, Desirée Bauer, Paola Arroyave, Sara Hernández, Maria A Martinez, Aida V Ralda, Neudy Rojop, Edgar E Barrios, Andrea Chacon, Walla Dempsey, Kay M Tomashek, Wendy A Keitel, Hana M El Sahly, Flor M Muñoz

Faculty, Staff and Students Publications

Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.

Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by …

Antibody Responses In Klebsiella Pneumoniae Bloodstream Infection: A Prospective Cohort Study, Wontae Hwang, Paeton L Wantuch, David A Rosen, Et Al.

2020-Current year OA Pubs

BACKGROUND: Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function.

METHODS: In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream …

Patient- And Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional …

Hospital-Onset Bacteremia In The Neonatal Intensive Care Unit: Strategies For Risk Adjustment, Erica C Prochaska, Shaoming Xiao, Elizabeth Colantuoni, Nora Elhaissouni, Reese H Clark, Julia Johnson, Sagori Mukhopadhyay, Ibukunoluwa C Kalu, Danielle M Zerr, Patrick J Reich, Jessica Roberts, Dustin D Flannery, Aaron M Milstone, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.

DESIGN: A retrospective, multicenter cohort study.

SETTING AND PARTICIPANTS: Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.

METHODS: Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based …

Rare Damaging Ccr2 Variants Are Associated With Lower Lifetime Cardiovascular Risk, Marios K Georgakis, Rainer Malik, Omar El Bounkari, Natalie R Hasbani, Jiang Li, Jennifer E Huffman, Gabrielle Shakt, Reinier W P Tack, Tamara N Kimball, Yaw Asare, Alanna C Morrison, Noah L Tsao, Renae Judy, Braxton D Mitchell, Huichun Xu, May E Montasser, Ron Do, Eimear E Kenny, Ruth J F Loos, James G Terry, John Jeffrey Carr, Joshua C Bis, Bruce M Psaty, W T Longstreth, Kendra A Young, Sharon M Lutz, Michael H Cho, Jai Broome, Alyna T Khan, Fei Fei Wang, Nancy Heard-Costa, Sudha Seshadri, Ramachandran S Vasan, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Lisa R Yanek, Brian G Kral, Lewis C Becker, Patricia A Peyser, Lawrence F Bielak, Farah Ammous, April P Carson, Michael E Hall, Laura M Raffield, Stephen S Rich, Wendy S Post, Russel P Tracy, Kent D Taylor, Xiuqing Guo, Michael C Mahaney, Joanne E Curran, John Blangero, Shoa L Clarke, Jeffrey W Haessler, Yao Hu, Themistocles L Assimes, Charles Kooperberg, Jürgen Bernhagen, Christopher D Anderson, Scott M Damrauer, Ramin Zand, Jerome I Rotter, Paul S De Vries, Martin Dichgans

Faculty, Staff and Student Publications

BACKGROUND: Previous work has shown a role of CCL2, a key chemokine governing monocyte trafficking, in atherosclerosis. However, it remains unknown whether targeting CCR2, the cognate receptor of CCL2, provides protection against human atherosclerotic cardiovascular disease.

METHODS: Computationally predicted damaging or loss-of-function (REVEL > 0.5) variants within CCR2 were detected in whole-exome-sequencing data from 454,775 UK Biobank participants and tested for association with cardiovascular endpoints in gene-burden tests. Given the key role of CCR2 in monocyte mobilization, variants associated with lower monocyte count were prioritized for experimental validation. The response to CCL2 of human cells transfected with these variants was tested …

Delivering Guideline-Directed Medical Therapy For Heart Failure With Reduced Ejection Fraction As An Over-Encapsulated Polypill: Rationale And Protocol For The Combo-Hf-X Pilot Crossover Randomised Clinical Trial, Colette Dejong, Mark D Huffman, Anubha Agarwal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: A four-drug regimen of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is underused, in part due to prescriber inertia and low patient adherence. Although fixed-dose combination pills ('polypills') have improved adherence and clinical outcomes for other conditions, there are no polypills available that combine multiple classes of GDMT for HFrEF. Pharmacy-level over-encapsulation, in which several tablets are combined into one capsule, offers an opportunity to create customised HFrEF polypills with the goal of improving delivery of HFrEF therapies.

METHODS AND ANALYSIS: In the COMBO-HF-X pilot crossover randomised clinical trial, we will enrol 30-40 patients …

Attitudes And Barriers Toward Antiretroviral Therapeutic Drug Monitoring Among Infectious Disease Providers, Hongmei Wang, Cecilia M Torres, Thomas P Giordano, Bich N Dang, Dong Liang

Faculty, Staff and Students Publications

Background/Objectives: Effective HIV treatment and prevention rely heavily on patient adherence to the prescribed regimen. Therapeutic drug monitoring (TDM), which involves measuring medication concentrations in blood circulation, offers an objective method to evaluate toxic or ineffective drug levels. TDM is not routinely used in HIV treatment in clinical practice. Therefore, the purpose of this study is to survey infectious disease providers’ attitudes and barriers toward therapeutic drug monitoring for antiretroviral therapy in people living with HIV. Materials and

Methods: A 15-item online survey was distributed to infectious disease providers in the Greater Houston area, including physicians, pharmacists, and mid-level practitioners …

Comparison Of Syndromic Surveillance And Hospital Discharge Data For Unintentional Drowning In Metropolitan Houston, Texas, Usa, Nicholas Peoples, Jennifer L Jones, Elizabeth A Camp, Ned Norman Levine, Rohit P Shenoi

Faculty, Staff and Students Publications

Background: Syndromic surveillance, which provides real-time data, may provide timely drowning surveillance compared with hospital discharge data where the release of data may be delayed. We compared data on hospital visits for unintentional drowning identified in hospital discharge and syndromic surveillance data sets for accuracy and completeness.

Methods: We compared data for hospital visits for unintentional drowning identified in the Texas Health Care Information Collection hospital discharge and syndromic surveillance data sets for metropolitan Houston, Texas, USA from 2019 to 2021. Hospital visits included emergency department-only visits and hospital admissions. We compared time-series visualisation of hospital visits between data sets. …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

2020-Current year OA Pubs

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Phase I Trial Of Tti-101, A First-In-Class Oral Inhibitor Of Stat3, In Patients With Advanced Solid Tumors, Apostolia M Tsimberidou, David J Vining, Sukeshi P Arora, Sofia De Achaval, Jeffrey Larson, John Kauh, Carrie Cartwright, Rony Avritscher, Imran Alibhai, David J Tweardy, Ahmed O Kaseb

Faculty, Staff and Student Publications

Purpose: Signal transducer and activator of transcription 3 is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in patients with advanced metastatic cancer.

Patients and methods: Patients were treated with TTI-101 orally twice daily in 28-day cycles at four dose levels (DL): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/day ("3+3" design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699).

Results: Sixty-four patients were treated (median …

Association Of Messenger Rna Coronavirus Disease 2019 (Covid-19) Vaccination And Reductions In Post Covid Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection In A Us Prospective Cohort Of Essential Workers, Josephine Mak, Sana Khan, Amadea Britton, Spencer Rose, Lisa Gwynn, Katherine D Ellingson, Jennifer Meece, Leora R Feldstein, Harmony Tyner, Laura J Edwards, Matthew S Thiese, Allison Naleway, Manjusha Gaglani, Natasha Solle, Jefferey L Burgess, Julie Mayo Lamberte, Meghan Shea, Taryn Hunt-Smith, Alberto Caban-Martinez, Cynthia Porter, Ryan Wiegand, Ramona Rai, Kurt T Hegmann, James Hollister, Ashley Fowlkes, Meredith Wesley, Andrew L Philips, Patrick Rivers, Robin Bloodworth, Gabriella Newes-Adeyi, Lauren E W Olsho, Sarang K Yoon, Sharon Saydah, Karen Lutrick

Center for Medical Ethics and Health Policy Staff Publications

Background: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Inflammation And Gut Barrier Function-Related Genes And Colorectal Cancer Risk In Western European Populations, Hannah B Mandle, Mazda Jenab, Marc J Gunter, Anne Tjønneland, Anja Olsen, Christina C Dahm, Jie Zhang, Pierre-Emmanuel Sugier, Joseph Rothwell, Gianluca Severi, Rudolf Kaaks, Verena A Katzke, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Carlotta Sacerdote, Catalina Bonet, Maria-Jose Sánchez, Pilar Amiano, José María Huerta, Marcela Guevara, Richard Palmqvist, Thyra Löwenmark, Aurora Perez-Cornago, Elisabete Weiderpass, Alicia K Heath, Amanda J Cross, Paolo Vineis, David J Hughes, Veronika Fedirko

Faculty, Staff and Student Publications

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-Of-Life Evaluation And 2-Year Outcomes Of Bmt Ctn 1703., Shernan G Holtan, Javier Bolaños-Meade, Monzr M Al Malki, Juan Wu, Carrie L Kitko, Ran Reshef, Andrew R Rezvani, Brian C Shaffer, Melhem M Solh, Janny M Yao, Lyndsey Runaas, Hany Elmariah, Karilyn T Larkin, Najla El Jurdi, Mahasweta Gooptu, Alison W Loren, Aric C Hall, Amin M Alousi, Omer Jamy, William Clark, Leslie Kean, Ami S Bhatt, Miguel-Angel Perales, Kristy Applegate, Yvonne Adeduni Efebera, Eric Leifer, Richard J Jones, Mary M Horowitz, Deborah Mattila, Wael Saber, Mehdi Hamadani, Michael J Martens

Oncology Articles

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant. PRO scores …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Trends In Respiratory Pathogen Testing At Us Children's Hospitals., Matthew J. Molloy, Matthew Hall, Jessica L. Markham, Jillian M. Cotter, Elisha Mccoy, Michael J. Tchou, Megan E. Collins, Michael J. Steiner, John R. Stephens, Andrew G. Yu, Irma T. Ugalde, Rustin B. Morse, Monika K. Goyal, Samantha A. House

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory pathogen testing has been a common deimplementation focus. The COVID-19 pandemic brought new considerations for respiratory testing; recent trends in testing rates are not well understood.

OBJECTIVE: To measure trends in respiratory testing among encounters for acute respiratory infections among children and adolescents (agedyears) from 2016 to 2023, assess the association of COVID-19 with these trends, and describe associated cost trends.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective serial cross-sectional study included emergency department (ED) encounters and hospitalizations in US children's hospitals among children and adolescents with a primary acute infectious respiratory illness diagnosis. Data were ascertained from the …

Cervical Necrotizing Fasciitis And Shock In The Post-Operative Pediatric Patient., Paul Bryan Hankey, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Cervical necrotizing fasciitis (CNF) is a rare infection that can quickly lead to devastating patient outcomes. Considering the vital importance of surrounding neck structures, rapid control of the infection is essential. Infection is most frequently polymicrobial and occurs in the adult patient in the context of certain medical comorbidities. Complications are typically limited to tissue destruction in the form of necrosis. There are no current reports describing CNF complicated by acute shock in the post-operative pediatric patient. Here, we present a pediatric case of CNF complicated by acute shock following Sistrunk procedure for removal of a supposed thyroglossal duct cyst. …

Prevention And Management Of Infectious Complications In Pediatric Patients With Cancer: A Survey Assessment Of Current Practices Across Children's Oncology Group Institutions., Leonora R. Slatnick, David Hoogstra, Brian T. Fisher, Joshua Wolf, Etan Orgel, C Nathan Nessle, Pratik A. Patel, Tamara P. Miller, Jennifer Wilkes, L Lee Dupuis, Erin Goode, Kasey Jackson, Daniel N. Willis, Caitlin Elgarten, Catherine Aftandilian, Joel Thompson, Sarah Alexander, Melissa P. Beauchemin, Jennifer A. Belsky, Jennifer Hess, Zachary D. Prudowsky, Terri Guinipero, Jenna Rossoff, Jenna Demedis, Alexandra M. Walsh, Rebecca Richards, Daniel K. Choi, Christopher C. Dvorak, Adam J. Esbenshade

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

METHODS: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

RESULTS: The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most …